Leuprolide Acetate Prevents Toxic Effects of Cisplatin on The Kidneys and Gastrointestinal Tract

Abstract

We examined the protective effects of medical castration by means of gonadotropin-releasing hormone analogue (GnRH_A) on the toxic effects of cisplatin in rats. Twelve days after a s.c. injection of a slowly-releasable form of leuprolide acetate (GnRH_ASR), rats were injected i.p. with cisplatin daily (3 mg/kg body weight (BW) for males and 4mg/kg BW for females) for four days and sacrificed 24h after the last injection. The doses caused acute tubular necrosis and gastrointestinal (GI) symptoms, i.e., diarrhea and fluid retention and bleeding in GI tract. GnRH_ASR pretreatment reduced serum urea nitrogen (SUN) and serum creatinine (SCre) increase and the incidence of GI symptoms. Histological analysis showed that rats pretreated with GnRH_ASR had noticeably less kidney damage. GnRH_A thus demonstrated its ability to protect the kidneys and GI tract against cisplatin toxicity in both male and female rats. This finding suggests a potential clinical application of GnRH_A in antineoplastic chemotherapy.